BLOOD CLOT FILTER WITH LOCAL THROMBOLYTIC DRUG DELIVERY
A thrombus capture and lysis device including a filter sized to be implanted within a blood vessel. The filter includes a plurality of hollow elements defining a mesh sized to span an area of the blood vessel. Each of the plurality of hollow elements defines a plurality of pores being sized to allow passage of a thrombolytic drug out through the pores and to prevent a thrombus forming component from entering the pores.
This application is related to and claims priority to U.S. Provisional Patent Application Ser. No. 62/332,609, filed May 6, 2016, entitled BLOOD CLOT FILTER WITH LOCAL THROMBOLYTIC DRUG DELIVERY, the entirety of which is incorporated herein by reference.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENTn/a
TECHNICAL FIELDThe present disclosure relates to an indwelling blood clot filter that catches a blood clot, also referred to as thrombus, in flowing blood.
BACKGROUNDFilters can be placed in blood vessels to catch thrombus carried in the flowing blood. Such filters have been used clinically for many years. Filters are primarily placed temporarily during a high-risk procedure. One of the problems with long-term placement of a clot filter is what happens to the thrombus after the clot thrombus been caught in the filter. Where a filter is placed temporarily, the thrombus typically is removed by removing the filter. However, a long-term indwelling filter is not easily removed.
Blood clots can be dissolved in patients that develop them; however, this is done with significant risk to the patient when aggressive thrombolytic drugs are used. Among the risks is the possibility that the clot can move to the brain and cause a stroke, or move to other parts of the body and result in an embolism. Thrombolytic drugs can be administered to the patient, and are sometimes effective in dissolving a clot in place. However, the thrombolytic drug enters the patient's bloodstream and thus can create a risk of a bleeding event, such as a hemorrhagic stroke.
SUMMARYThe present application advantageously provides for a thrombus capture and lysis device including a filter sized to be implanted within a blood vessel. The filter includes a plurality of hollow elements defining a mesh sized to span an area of the blood vessel. Each of the plurality of hollow elements defines a plurality of pores being sized to allow passage of a thrombolytic drug out through the plurality of pores and to prevent a thrombus forming component from entering the plurality pores.
In another aspect of this embodiment, each of the plurality of hollow elements are in fluid communication with each other.
In another aspect of this embodiment, the device includes a dispenser configured dispense the thrombolytic drug, the dispenser being in fluid communication with the plurality of hollow elements.
In another aspect of this embodiment, the plurality of hollow elements defines a substantially conical shape.
In another aspect of this embodiment, the plurality of hollow elements defines an oblique angle.
In another aspect of this embodiment, the mesh defines a plurality of gaps between adjacent hollow elements, wherein each gap defines a diameter, the diameter of the gap being smaller than a diameter of the thrombus forming components.
In another aspect of this embodiment, the filter includes a first surface and an opposite second surface, and wherein the plurality of pores are entirely disposed on the first surface.
In another aspect of this embodiment, the filter includes a first portion and a second portion, and wherein the second portion is configured to be positioned downstream of the first portion when the filter is implanted within the blood vessel, and where in the second portion includes at least one from the group consisting of more pores, larger pores, and both larger pores and more pores than the first portion.
In another aspect of this embodiment, the thrombus forming component is fibrinogen.
In another aspect of this embodiment, the thrombolytic drug is tissue plasminogen activator.
In another aspect of this embodiment, the plurality the pores have an average pore size of between 5 and 10 nm.
In another embodiment, a thrombus capture and lysis device includes a filter sized to be implanted within a blood vessel. The filter includes a plurality of hollow elements defining a mesh sized to span an area of the blood vessel. Each of the plurality of hollow elements defines a plurality of pores, the plurality of pores being sized to allow passage of a thrombolytic drug out through the plurality of pores and to prevent a thrombus forming component from entering the plurality of pores. A plurality of sensors coupled to the filter are included, the plurality of sensors being configured to detect the presence of the thrombus forming component and to initiate a release of the thrombolytic drug.
In another aspect of this embodiment, the device includes a dispenser in fluid communication with the hollow elements and in communication with the plurality of sensors, the dispenser retaining a volume of the thrombolytic drug.
In another aspect of this embodiment, the dispenser includes a plurality of selectively operable microdispensers disposed at different locations on the filter.
In another aspect of this embodiment, the device includes a control circuit operatively connected to the plurality of sensors and microdispensers, the control circuit being operative to actuate a respective microdispenser proximate a respective one of the plurality of sensors when the presence of thrombus forming component is detected by the respective one of the plurality of sensors.
In another aspect of this embodiment, the filter includes a first surface and an opposite second surface, and wherein the plurality of pores are entirely disposed on the first surface.
In another aspect of this embodiment, the filter includes a first portion and a second portion, and wherein the second portion is configured to be positioned downstream of the first portion when the filter is implanted within the blood vessel, and where in the second portion includes at least one from the group consisting of more pores, larger pores, and both larger pores and more pores than the first portion.
In another aspect of this embodiment, the thrombus forming component is fibrinogen.
In another aspect of this embodiment, the thrombolytic drug is tissue plasminogen activator.
In yet another embodiment, a thrombus capture and lysis device includes a filter sized to be implanted within a blood vessel. The filter includes a plurality of hollow elements defining a mesh sized to span an area of the blood vessel. Each of the plurality of hollow elements defining a plurality of pores. The plurality of pours being sized to allow passage of a thrombolytic drug out through the plurality of pores and to prevent fibrinogen from entering the plurality of pores. The filter includes a first portion and a second portion, and the second portion is configured to be positioned downstream of the first portion when the filter is implanted within the blood vessel, and the second portion includes at least one from the group consisting of more pores, larger pores, and both larger pores and more pores than the first portion. The filter further includes a first surface and an opposite second surface, and the plurality of pores are entirely disposed on the first surface. A plurality of sensors is coupled to the first surface of the filter at a plurality of different locations. The plurality of sensors being configured to detect the presence of fibrinogen and to initiate a release of the thrombolytic drug. A plurality of selectively operable microdispensers are in fluid communication with the hollow elements and in communication with the plurality of sensors, the plurality of microdispensers retaining a volume of the thrombolytic drug. A control circuit is operatively connected to the plurality of sensors and microdispensers, the control circuit being operative to actuate a respective microdispenser proximate a respective one of the plurality of sensors when the presence of fibrinogen is detected by the respective one of the plurality of sensors.
A more complete understanding of the present invention, and the attendant advantages and features thereof, will be more readily understood by reference to the following detailed description when considered in conjunction with the accompanying drawings wherein:
Referring now to the drawings in which like reference designators refer to like elements, there is shown in
The filter 14 as a whole defines a front surface 28, which is the surface of the filter 14 facing toward the viewer in
The interior spaces 20 within some or all of the hollow elements 18 are connected in communication with a source of a thrombolytic drug 30 (
In one configuration, the pores 24 (
One common thrombolytic drug is tissue plasminogen activator (“tPA”). tPA is a protein having a mass of 72 kilo Daltons and having a globular form. The estimated diameter of the tPA molecule is 5.5 nm, based on the relationship
Radiusmin=0.066 m1/3 (Formula 1)
where m is the mass of the protein in Daltons, Radiusmin is the radius of the protein molecule in nm. This relationship assumes that the protein molecule has a spherical configuration, which is reasonable given its globular form.
The estimating technique set forth in Formula 1, and other techniques for estimating and measuring the size of protein molecules are known in the art. See Erickson H. P., Size and Shape of Protein Molecules at the Nanometer Level Determined by Sedimentation, Gel Filtration, and Electron Microscopy, Shulin Li (ed.), Biological Procedures Online, Volume 11, Number 1 (2009), the disclosure of which is incorporated herein by reference. Fibrinogen, a thrombus-forming molecule present in blood, has an atomic mass of 340 kilo Daltons. Based on the relationship set forth in Formula 1 above, the fibrinogen molecule has an estimated diameter of 9.21 nm. Thus, to permit passage of tPA but block passage of fibrinogen, the pore 24 size should be between 5.5 nm and 9.2 nm, and in some configurations between 5 and 10 nm. Platelets, another constituent of blood involved in thrombus formation, are cell fragments having an average diameter of 2 μm, i.e., 2000 nm. Thus, a pore 24 size between 5.5 nm and 2000 nm would permit passage of tPA but block passage of platelets. One method of making hollow fibers with pore sizes as small as 5 nm is disclosed in U.S. Pat. No. 4,405,688, the disclosure of which is incorporated herein as a part of this disclosure. The appropriate pore 24 size for use with thrombolytic drugs other than tPA can be estimated in a similar manner using the technique of Formula 1 or other known estimating or measuring techniques. Any thrombolytic drug can be used. Common thrombolytic drugs include anistreplase, streptokinase, kabikinase, urokinase, reteplase, tenecteplase, and rokinase, as well as tPA. One thrombolytic drug, or a combination of thrombolytic drugs may be used. The hollow elements 16 can be formed from polymeric materials compatible with blood, as, for example, polyolefins such as polymethylpentene and polypropylene. These materials have been used in contact with blood in devices such as oxygenators.
In a method of operation according to a further embodiment of the disclosure, the device 10 is implanted in the blood vessel and connected to the source of tPA or other thrombolytic drug as discussed above. While the device 10 is in place, blood passes through gaps 26 in the filter 14 and flows in the downstream direction. Thrombus T, carried by the blood, may deposit on filter 14, abutting the outer surfaces 22 of the hollow elements 16. Source 30 may be actuated to deliver the thrombolytic drug at slow, steady rate, or may be actuated periodically. The thrombolytic drug passing out of the pores 24 in the vicinity of the clot contacts the clot at or near the interface between the clot and the hollow element 16, and thus dissolves the clot from the bottom up.
In a further embodiment of the disclosure, the walls 18 of the fibers or other hollow elements can be formed as solid membranes, without discrete pores 24. The membrane material is selected so that it is permeable to the thrombolytic drug. The thrombolytic drug will move through the membrane in a diffusion process driven by osmotic pressure, fluid pressure maintained in the interior spaces of the hollow elements 16, or both. The material of the membrane may be selected to have greater permeability to the thrombolytic drug than to thrombus-forming constituents of the blood.
Referring now to
Referring now to
As discussed above, it is advantageous to deliver the drug through the hollow elements 16 constituting the filter 14. However, in other embodiments, the drug may be delivered in proximity to the filter 14 by other methods and structures. For example, the drug 30 source may be connected to a tubular element (not shown) having a single outlet port, or a small number of outlet ports, upstream of the filter front surface, or within the filter.
According to a further aspect of the disclosure, the thrombolytic drug can be delivered in response to detection of thrombus accumulated on the filter. This arrangement is shown in the flow chart of
Referring now to
Referring now to
Referring now to
In the discussion above, devices according to certain aspects of the present disclosure have been referred to as intravascular devices, and have been described as implanted within blood vessels. However, devices according to the present disclosure also can be installed in prosthetic devices that form part of the circulatory system as and carry flowing blood. For example, filters 14 according to the present disclosure may be installed in or on blood-carrying passages of devices such as blood pumps used as elements of mechanical circulatory support devices, also referred to as ventricular assist devices or “VADs”, or in conduits used to connect such pumps to the native circulatory system of the patient. In such an arrangement, the structure used to mount the filter may be arranged for attachment to the prosthetic device, or may be part of the prosthetic device itself. Further, filters 14 according to the present disclosure may be mounted within the heart itself. The term “circulatory element” as used herein includes both natural blood vessels and the heart, as well as passages or chambers of a prosthetic device that, when installed, forms a part of the circulatory system.
Claims
1. A thrombus capture and lysis device, comprising:
- a filter sized to be implanted within a blood vessel, the filter including a plurality of hollow elements defining a mesh sized to span an area of the blood vessel, each of the plurality of hollow elements defining a plurality of pores, the plurality of pores being sized to allow passage of a thrombolytic drug out through the plurality of pores and to prevent a thrombus forming component from entering the plurality of pores.
2. The device of claim 1, wherein each of the plurality of hollow elements are in fluid communication with each other.
3. The device of claim 1, further including a dispenser configured dispense the thrombolytic drug, the dispenser being in fluid communication with the plurality of hollow elements.
4. The device of claim 1, wherein the plurality of hollow elements defines a substantially conical shape.
5. The device of claim 1, wherein the plurality of hollow elements defines an oblique angle.
6. The device of claim 1, wherein the mesh defines a plurality of gaps between adjacent hollow elements, wherein each gap defines a diameter, the diameter of the gap being smaller than a diameter of the thrombus forming components.
7. The device of claim 1, wherein the filter includes a first surface and an opposite second surface, and wherein the plurality of pores are entirely disposed on the first surface.
8. The device of claim 1, wherein the filter includes a first portion and a second portion, and wherein the second portion is configured to be positioned downstream of the first portion when the filter is implanted within the blood vessel, and where in the second portion includes at least one from the group consisting of more pores, larger pores, and both larger pores and more pores than the first portion.
9. The device of claim 1, wherein the thrombus forming component is fibrinogen.
10. The device of claim 1, wherein the thrombolytic drug is tissue plasminogen activator.
11. The device of claim 1, wherein the plurality the pores have an average pore size of between 5 and 10 nm.
12. A thrombus capture and lysis device, comprising:
- a filter sized to be implanted within a blood vessel, the filter including a plurality of hollow elements defining a mesh sized to span an area of the blood vessel, each of the plurality of hollow elements defining a plurality of pores, the plurality of pores being sized to allow passage of a thrombolytic drug out through the plurality of pores and to prevent a thrombus forming component from entering the plurality of pores; and
- a plurality of sensors coupled to the filter, the plurality of sensors being configured to detect the presence of the thrombus forming component and to initiate a release of the thrombolytic drug.
13. The device of claim 12, further including a dispenser in fluid communication with the hollow elements and in communication with the plurality of sensors, the dispenser retaining a volume of the thrombolytic drug.
14. The device of claim 13, wherein the dispenser includes a plurality of selectively operable microdispensers disposed at different locations on the filter.
15. The device of claim 14, further comprising a control circuit operatively connected to the plurality of sensors and microdispensers, the control circuit being operative to actuate a respective microdispenser proximate a respective one of the plurality of sensors when the presence of thrombus forming component is detected by the respective one of the plurality of sensors.
16. The device of claim 12, wherein the filter includes a first surface and an opposite second surface, and wherein the plurality of pores are entirely disposed on the first surface.
17. The device of claim 12, wherein the filter includes a first portion and a second portion, and wherein the second portion is configured to be positioned downstream of the first portion when the filter is implanted within the blood vessel, and where in the second portion includes at least one from the group consisting of more pores, larger pores, and both larger pores and more pores than the first portion.
18. The device of claim 12, wherein the thrombus forming component is fibrinogen.
19. The device of claim 12, wherein the thrombolytic drug is tissue plasminogen activator.
20. A thrombus capture and lysis device, comprising:
- a filter sized to be implanted within a blood vessel, the filter including a plurality of hollow elements defining a mesh sized to span an area of the blood vessel, each of the plurality of hollow elements defining a plurality of pores, the plurality of pours being sized to allow passage of a thrombolytic drug out through the plurality of pores and to prevent fibrinogen from entering the plurality of pores;
- the filter including a first portion and a second portion, the second portion is configured to be positioned downstream of the first portion when the filter is implanted within the blood vessel, and the second portion includes at least one from the group consisting of more pores, larger pores, and both larger pores and more pores than the first portion; the filter further including a first surface and an opposite second surface, and the plurality of pores are entirely disposed on the first surface;
- a plurality of sensors coupled to the first surface of the filter at a plurality of different locations, the plurality of sensors being configured to detect the presence of fibrinogen and to initiate a release of the thrombolytic drug;
- a plurality of selectively operable microdispensers in fluid communication with the hollow elements and in communication with the plurality of sensors, the plurality of microdispensers retaining a volume of the thrombolytic drug; and
- a control circuit operatively connected to the plurality of sensors and microdispensers, the control circuit being operative to actuate a respective microdispenser proximate a respective one of the plurality of sensors when the presence of fibrinogen is detected by the respective one of the plurality of sensors.
Type: Application
Filed: May 4, 2017
Publication Date: Nov 9, 2017
Patent Grant number: 10687931
Inventor: Gill Brent Bearnson (Salt Lake City, UT)
Application Number: 15/586,675